The safety of tacrolimus ointment for the treatment of atopic dermatitis: A review

British Journal of Dermatology

Volumn 157, Issue 5, 2007, Pages 861-873

  Rustin, M H A ^a  

^a ROYAL FREE HOSPITAL   (United Kingdom)

Author keywords

Atopic dermatitis; Pimecrolimus; Safety; Tacrolimus ointment; Topical calcineurin inhibitors; Topical corticosteroids

Indexed keywords

BETAMETHASONE VALERATE; CORTICOSTEROID; HYDROCORTISONE ACETATE; HYDROCORTISONE BUTYRATE; PIMECROLIMUS; TACROLIMUS; TRIAMCINOLONE ACETONIDE;

ACNE; ALCOHOL INTOLERANCE; ASTHMA; ATOPIC DERMATITIS; BURNING SENSATION; CANCER INCIDENCE; CARCINOGENICITY; CLINICAL TRIAL; COLLAGEN SYNTHESIS; COLONY FORMING UNIT; COUGHING; DISEASE SEVERITY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERANCE; DRUG WITHDRAWAL; ERYTHEMA; FEVER; FLU LIKE SYNDROME; FOLLICULITIS; HERPES SIMPLEX; HUMAN; HYPERESTHESIA; IMMUNE RESPONSE; IMMUNOCOMPETENCE; NETHERTON DISEASE; NONHUMAN; PHARYNGITIS; PRESCRIPTION; PRIORITY JOURNAL; REVIEW; RISK; SKIN ATROPHY; SKIN CANCER; SKIN INFECTION; SKIN PRURITUS; SKIN TEST; SKIN TINGLING;

ADMINISTRATION, TOPICAL; DERMATITIS, ATOPIC; DERMATOLOGIC AGENTS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; OINTMENTS; SKIN NEOPLASMS; TACROLIMUS; TREATMENT OUTCOME;

EID: 35348904600     PISSN: 00070963     EISSN: 13652133     Source Type: Journal    
DOI: 10.1111/j.1365-2133.2007.08177.x     Document Type: Review

References (77)

1. Almawi WY, Melemedjian OK. Molecular mechanisms of glucocorticoid antiproliferative effects: antagonism of transcription factor activity by glucocorticoid receptor. J Leukoc Biol 2002 71:9 15.
2. Nghiem P, Pearson G, Langley RG. Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol 2002 46:228 41.
3. Kino T, Hatanaka H, Miyata S et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo) 1987 40:1256 65.
4. Liu J, Albers MW, Wandless TJ et al. Inhibition of T cell signaling by immunophilin-ligand complexes correlates with loss of calcineurin phosphatase activity. Biochemistry 1992 31:3896 901.
5. Kohyama T, Takizawa H, Kawasaki S et al. A potent immunosuppressant FK506 inhibits IL-8 expression in human eosinophils. Mol Cell Biol Res Commun 1999 1:72 7.
6. Sawada S, Suzuki G, Kawase Y et al. Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. J Immunol 1987 139:1797 803.
7. Sengoku T, Kishi S, Sakuma S et al. FK506 inhibition of histamine release and cytokine production by mast cells and basophils. Int J Immunopharmacol 2000 22:189 201.
8. Wollenberg A, Bieber T. Topical immunomodulatory agents and their targets in inflammatory skin diseases. Transplant Proc 2001 33:2212 6.
9. Beck LA. The efficacy and safety of tacrolimus ointment: a clinical review. J Am Acad Dermatol 2005 53:S165 70.
10. Hanifin JM, Ling MR, Langley R et al. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J Am Acad Dermatol 2001 44:S28 38.
11. Soter NA, Fleischer AB Jr., Webster GF et al. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part II, safety. J Am Acad Dermatol 2001 44:S39 46.
12. Paller A, Eichenfield LF, Leung DY et al. A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 2001 44:S47 57.
13. Reitamo S, Wollenberg A, Schopf E et al. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group. Arch Dermatol 2000 136:999 1006.
14. Kang S, Lucky AW, Pariser D et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 2001 44:S58 64.
15. Reitamo S, Rustin M, Ruzicka T et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis. J Allergy Clin Immunol 2002 109:547 55.
16. Reitamo S, van Leent EJ, Ho V et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis. J Allergy Clin Immunol 2002 109:539 46.
17. Reitamo S, Harper J, Bos JD et al. 0·03% tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial. Br J Dermatol 2004 150:554 62.
18. Reitamo S, Ortonne JP, Sand C et al. A multicentre, randomized, double-blind, controlled study of long-term treatment with 0·1% tacrolimus ointment in adults with moderate to severe atopic dermatitis. Br J Dermatol 2005 152:1282 9.
19. Koo JY, Fleischer AB Jr., Abramovits W et al. Tacrolimus ointment is safe and effective in the treatment of atopic dermatitis: results in 8000 patients. J Am Acad Dermatol 2005 53:S195 205.
20. Hanifin JM, Paller AS, Eichenfield L et al. Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol 2005 53:S186 94.
21. Schachner LA, Lamerson C, Sheehan MP et al. Tacrolimus ointment 0·03% is safe and effective for the treatment of mild to moderate atopic dermatitis in pediatric patients: results from a randomized, double-blind, vehicle-controlled study. Pediatrics 2005 116:e334 42.
22. Remitz A, Harper J, Rustin M, on behalf of the European Tacrolimus Ointment Study Group. The long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. Acta Derm Venereol (Stockh) 2007 87:54 61.
23. Nakagawa H. Comparison of the efficacy and safety of 0·1% tacrolimus ointment with topical corticosteroids in adult patients with atopic dermatitis: review of randomised, double-blind clinical studies conducted in Japan. Clin Drug Invest 2006 26:235 46.
24. Paller AS, Lebwohl M, Fleischer AB Jr. et al. Tacrolimus ointment is more effective than pimecrolimus cream with a similar safety profile in the treatment of atopic dermatitis: results from 3 randomized, comparative studies. J Am Acad Dermatol 2005 52:810 22.
25. Kempers S, Boguniewicz M, Carter E et al. A randomized investigator-blinded study comparing pimecrolimus cream 1% with tacrolimus ointment 0·03% in the treatment of pediatric patients with moderate atopic dermatitis. J Am Acad Dermatol 2004 51:515 25.
26. U.S. Food and Drug Administration. Alert for Healthcare Professionals. Tacrolimus (marketed as Protopic). FDA Alert 3/2005. Available at: http://www.fda.gov/cder/drug/InfoSheets/HCP/protopicHCP.htm (accessed 5 July 2007).
27. Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation 2005 80:S254 64.
28. Astellas Pharma GmbH. Summaries of Product Characteristics. Protopic 0·03% Ointment and Protopic 0·1% Ointment. Munich, Germany:Astellas Pharma GmbH, 2006.
29. Patel RR, Vander Straten MR, Korman NJ. The safety and efficacy of tacrolimus therapy in patients younger than 2 years with atopic dermatitis. Arch Dermatol 2003 139:1184 6.
30. Alaiti S, Kang S, Fiedler VC et al. Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children. J Am Acad Dermatol 1998 38:69 76.
31. Ruzicka T, Bieber T, Schopf E et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group. N Engl J Med 1997 337:816 21.
32. Boguniewicz M, Fiedler VC, Raimer S et al. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children. Pediatric Tacrolimus Study Group. J Allergy Clin Immunol 1998 102:637 44.
33. Harper J, Smith C, Rubins A et al. A multicenter study of the pharmacokinetics of tacrolimus ointment after first and repeated application to children with atopic dermatitis. J Invest Dermatol 2005 124:695 9.
34. Rubins A, Gutmane R, Valdmane N et al. Pharmacokinetics of 0·1% tacrolimus ointment after first and repeated application to adults with moderate to severe atopic dermatitis. J Invest Dermatol 2005 125:68 71.
35. Tonin E, Varagnolo C, Pigozzi B et al. Tacrolimus blood levels after 3 months repeated application to children with atopic dermatitis. J Eur Acad Dermatol Venereol 2005 19 (Suppl. 2 150 (abstract).
36. Tonin E, Pigozzi B, Fortina AB. Does prolonged topical application of tacrolimus in children result in systemic accumulation J Invest Dermatol 2005 125:613.
37. Reitamo S, Rubins A, Ho V et al. Pharmacokinetics of topical tacrolimus in paediatric patients aged 3 to 24 months. Presented at the 15th Congress of the European Academy of Dermatology and Venereology, Rhodes, Greece, 2006.
38. Bos JD. Non-steroidal topical immunomodulators provide skin-selective, self-limiting treatment in atopic dermatitis. Eur J Dermatol 2003 13:455 61.
39. Kawashima M, Harada S, Tamaki K. A safety study of FK506 ointment in patients with atopic dermatitis. J Clin Ther Med 1997 13:1483 92.
40. Allen A, Siegfried E, Silverman R et al. Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Arch Dermatol 2001 137:747 50.
41. Briggs WA, Eustace J, Gimenez LF et al. Lymphocyte suppression by glucocorticoids with cyclosporine, tacrolimus, pentoxifylline, and mycophenolic acid. J Clin Pharmacol 1999 39:125 30.
42. Wong PY, Marinos G, Peakman M et al. FK506 in liver transplantation for chronic hepatitis B: in vitro studies on lymphocyte activation and virus replication. Liver Transpl Surg 1995 1:362 70.
43. Hanifin JM, Chan SC. Monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis. J Invest Dermatol 1995 105:S84 8.
44. Strannegård Ö, Strannegård I-L. Changes in cell-mediated immunity in atopic eczema. In:Handbook of Atopic Eczema (Ruzicka T, Ring J, Przybilla B, eds). Berlin:Springer-Verlag, 1991 54 79.
45. Homey B, Assmann T, Vohr HW et al. Topical FK506 suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during primary skin immune responses. J Immunol 1998 160:5331 40.
46. Alomar A, Berth-Jones J, Bos JD et al. The role of topical calcineurin inhibitors in atopic dermatitis. Br J Dermatol 2004 151 (Suppl. 70 3 27.
47. Pournaras CC, Lubbe J, Saurat JH. Staphylococcal colonization in atopic dermatitis treatment with topical tacrolimus (Fk506). J Invest Dermatol 2001 116:480 1.
48. Remitz A, Kyllonen H, Granlund H et al. Tacrolimus ointment reduces staphylococcal colonization of atopic dermatitis lesions. J Allergy Clin Immunol 2001 107:196 7.
49. Park CW, Lee BH, Lee CH. Tacrolimus reduces staphylococcal colonization on the skin in Korean atopic dermatitis patients. Drugs Exp Clin Res 2005 31:77 87.
50. Fleischer AB Jr., Ling M, Eichenfield L et al. Tacrolimus ointment for the treatment of atopic dermatitis is not associated with an increase in cutaneous infections. J Am Acad Dermatol 2002 47:562 70.
51. Stiehm ER, Roberts RL, Kaplan MS et al. Pneumococcal seroconversion after vaccination for children with atopic dermatitis treated with tacrolimus ointment. J Am Acad Dermatol 2005 53:S206 13.
52. Hofman T, Cranswick N, Kuna P et al. Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children. Arch Dis Child 2006 91:905 10.
53. U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Elidel (Pimecrolimus) Cream. Company: Novartis Pharmaceuticals Corporation. Application No.: 21-302. Approval date: 13 December 2001. Available at: http://www.fda.gov/cder/foi/nda/2001/21-302_Elidel.htm (accessed 5 July 2007).
54. Tran C, Lubbe J, Sorg O et al. Topical calcineurin inhibitors decrease the production of UVB-induced thymine dimers from hairless mouse epidermis. Dermatology 2005 211:341 7.
55. Jiang H, Yamamoto S, Nishikawa K, Kato R. Anti-tumor-promoting action of FK506, a potent immunosuppressive agent. Carcinogenesis 1993 14:67 71.
56. Niwa Y, Terashima T, Sumi H. Topical application of the immunosuppressant tacrolimus accelerates carcinogenesis in mouse skin. Br J Dermatol 2003 149:960 7.
57. Carroll CL, Fleischer AB Jr. Tacrolimus: focusing on atopic dermatitis. Drugs Today (Barc) 2006 42:431 9.
58. Ring J, Barker J, Behrendt H et al. Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum. J Eur Acad Dermatol Venereol 2005 19:663 71.
59. Bieber T, Cork M, Ellis C et al. Consensus statement on the safety profile of topical calcineurin inhibitors. Dermatology 2005 211:77 8.
60. Richardson K. Topical pimecrolimus, tacrolimus, and the risk for cancer: an expert interview with Lawrence Eichenfield, MD. Medscape Dermatol 2005 6. Available at: http://www.medscape.com/viewarticle/502337 (accessed 1 September 2007).
61. Fonacier L, Spergel J, Charlesworth EN et al. Report of the Topical Calcineurin Inhibitor Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2005 115:1249 53.
62. Ormerod AD. Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern? Br J Dermatol 2005 153:701 5.
63. Berger TG, Duvic M, van Voorhees AS et al. The use of topical calcineurin inhibitors in dermatology: safety concerns. Report of the American Academy of Dermatology Association Task Force. J Am Acad Dermatol 2006 54:818 23.
64. Fleischer AB Jr. Show me the signal, FDA. Skin Allergy News 2005 36:10.
65. Naylor M, Elmets C, Jaracz E et al. Non-melanoma skin cancer in patients with atopic dermatitis treated with topical tacrolimus. J Dermatol Treat 2005 16:149 53.
66. Frieling UM, Schaumberg DA, Kupper TS et al. A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study. Arch Dermatol 2000 136:179 84.
67. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology 2007 214:289 95.
68. Arellano FM, Wentworth CE, Arana A et al. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol 2007 127:808 16.
69. Spergel J, Prenner B, Rico MJ. Tacrolimus ointment is a safe and effective treatment for mild atopic dermatitis. J Allergy Clin Immunol 2003 115:S367 (abstract P349).
70. Chapman MS, Schachner LA, Breneman D et al. Tacrolimus ointment 0·03% shows efficacy and safety in pediatric and adult patients with mild to moderate atopic dermatitis. J Am Acad Dermatol 2005 53:S177 85.
71. Korting HC, Unholzer A, Schafer-Korting M et al. Different skin thinning potential of equipotent medium-strength glucocorticoids. Skin Pharmacol Appl Skin Physiol 2002 15:85 91.
72. Brazzini B, Pimpinelli N. New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use. Am J Clin Dermatol 2002 3:47 58.
73. Hughes J, Rustin M. Corticosteroids. Clin Dermatol 1997 15:715 21.
74. Haapasaari KM, Risteli J, Oikarinen A. Recovery of human skin collagen synthesis after short-term topical corticosteroid treatment and comparison between young and old subjects. Br J Dermatol 1996 135:65 9.
75. Reitamo S, Rissanen J, Remitz A et al. Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized trial. J Invest Dermatol 1998 111:396 8.
76. Queille-Roussel C, Paul C, Duteil L et al. The new topical ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study. Br J Dermatol 2001 144:507 13.
77. Kyllonen H, Remitz A, Mandelin JM et al. Effects of 1-year intermittent treatment with topical tacrolimus monotherapy on skin collagen synthesis in patients with atopic dermatitis. Br J Dermatol 2004 150:1174 81.